4749 total record number 121 records this year

Checkpoint Receptor TIGIT Expressed on Tim-1+ B Cells Regulates Tissue Inflammation

Xiao, S;Bod, L;Pochet, N;Kota, SB;Hu, D;Madi, A;Kilpatrick, J;Shi, J;Ho, A;Zhang, H;Sobel, R;Weiner, HL;Strom, TB;Quintana, FJ;Joller, N;Kuchroo, VK;

Tim-1, a phosphatidylserine receptor expressed on B cells, induces interleukin 10 (IL-10) production by sensing apoptotic cells. Here we show that mice with B cell-specific Tim-1 deletion develop tissue inflammation in multiple organs including spontaneous paralysis with inflammation in the central nervous system (CNS). Transcriptomic analysis demonstrates that besides IL-10, Tim-1+ B cells also differentially express a number of co-inhibitory checkpoint receptors including TIGIT. Mice with B cell-specific TIGIT deletion develop spontaneous paralysis with CNS inflammation, but with limited inflammation in other organs. Our findings suggest that Tim-1+ B cells are essential for maintaining self-tolerance and restraining tissue inflammation, and that Tim-1 signaling-dependent TIGIT expression on B cells is essential for maintaining CNS-specific tolerance. A possible critical role of aryl hydrocarbon receptor (AhR) in regulating the B cell function is discussed, as we find that AhR is among the preferentially expressed transcription factors in Tim-1+ B cells and regulates their TIGIT and IL-10 expression.